N-乙酰基氨力农 | 62749-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: N-乙酰基氨力农
• 英文名称: N-Acetylamrinone
• 英文别名: 5-acetylamino-1H-[3,4']bipyridinyl-6-one；N-[1,2-dihydro-2-oxo-5-(4-pyridinyl)-3-pyridinyl]acetamide；N-(2-oxo-5-pyridin-4-yl-1H-pyridin-3-yl)acetamide
• CAS: 62749-47-7
• 化学式: C₁₂H₁₁N₃O₂
• 分子量: 229.238
• InChiKey: QJXRAYQFXMRDHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  氨力农 在 吡啶 、 乙酸酐 作用下， 生成 N-乙酰基氨力农
  参考文献：
  名称：

  3-Cyano-5-(pyridinyl)-2(1H)-pyridinones

  摘要：

  作为心力衰竭药物有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮(I)，其中R是氢、较低的烷基或较低的羟基烷基，Q是氨基（首选）或NHAc，Ac是较低的烷酰基或较低的羧酰基，PY是带有一个或两个较低烷基取代基的4-、3-或2-吡啶基或4-、3-或2-吡啶基。相应的化合物中，Q为硝基、氨基甲酰基、氰基或氢的化合物可用作中间体，Q为氢或氰基的化合物也可用作心力衰竭药物。所述化合物通过以下方法制备：通过将α-PY-β-(R1R2N)丙烯醛(II)与马来酰胺反应，生成1,2-二氢-2-氧代-5-PY-烟酰胺(Ia)，然后将Ia与能够将氨基转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮(Ib)；通过将II或α-PY-马隆醛(II')与α-氰基乙酰胺反应，生成1,2-二氢-2-氧代-5-PY-烟酰腈(III)，部分水解III生成Ia；通过将1,2-二氢-2-氧代-5-PY-烟酸(IV)与浓硫酸和浓硝酸混合加热，生成3-硝基-5-PY-2(1H)-吡啶酮(Ic)，然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮(Id)，再将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮(Ib)，其中R'是较低的烷基或较低的羟基烷基。

  公开号：

  US04004012A1

文献信息

• 5-(Pyridinyl)-2(1H)-pyridinones
  申请人：Sterling Drug Inc.

  公开号：US04107315A1

  公开（公告）日：1978-08-15

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.

  作为心力衰竭药物有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮（I），其中R是氢、低烷基或低羟基烷基，Q是氨基（首选）、低烷基氨基、二（低烷基）氨基或NHAc，Ac是低脂肪酰基或低羰基脂肪酸酯，PY是具有一个或两个低烷基取代基的4-或3-或2-吡啶基或4-或3-或2-吡啶基。Q为硝基、氨基甲酰基、氰基、卤素或氢的相应化合物可用作中间体，Q为氢或氰基的化合物也可用作心力衰竭药物。所述化合物的制备方法包括：通过将.alpha.-PY-.beta.-(R1R2N)丙烯醛（II）与马来酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰胺（Ia），然后将Ia与能够将氨基甲酰转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮（Ib）；通过将II或.alpha.-PY-马隆醛（II'）与.alpha.-氰基乙酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰腈（III），然后部分水解III，生成Ia；通过将1,2-二氢-2-氧-5-PY-烟酸（IV）与浓硫酸和浓硝酸的混合物加热，生成3-硝基-5-PY-2(1H)-吡啶酮（Ic），然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮（Id），再将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮（Ib），其中R'是低烷基或低羟基烷基。显示了Q为氨基的I的其他衍生物。
• 3-Cyano-5-(pyridinyl)-2(1H)-pyridinones
  申请人：Sterling Drug Inc.

  公开号：US04004012A1

  公开（公告）日：1977-01-18

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, loweralkyl or lower-hydroxyalkyl, Q is amino (preferred) or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl.

  作为心力衰竭药物有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮(I)，其中R是氢、较低的烷基或较低的羟基烷基，Q是氨基（首选）或NHAc，Ac是较低的烷酰基或较低的羧酰基，PY是带有一个或两个较低烷基取代基的4-、3-或2-吡啶基或4-、3-或2-吡啶基。相应的化合物中，Q为硝基、氨基甲酰基、氰基或氢的化合物可用作中间体，Q为氢或氰基的化合物也可用作心力衰竭药物。所述化合物通过以下方法制备：通过将α-PY-β-(R1R2N)丙烯醛(II)与马来酰胺反应，生成1,2-二氢-2-氧代-5-PY-烟酰胺(Ia)，然后将Ia与能够将氨基转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮(Ib)；通过将II或α-PY-马隆醛(II')与α-氰基乙酰胺反应，生成1,2-二氢-2-氧代-5-PY-烟酰腈(III)，部分水解III生成Ia；通过将1,2-二氢-2-氧代-5-PY-烟酸(IV)与浓硫酸和浓硝酸混合加热，生成3-硝基-5-PY-2(1H)-吡啶酮(Ic)，然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮(Id)，再将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮(Ib)，其中R'是较低的烷基或较低的羟基烷基。
• PYRID-2-ONES USEFUL AS INHIBITORS OF TEC FAMILY PROTEIN KINASES FOR THE TREATMENT OF INFLAMMATORY, PROLIFERATIVE AND IMMUNOLOGICALLY-MEDIATED DISEASES.
  申请人：Vertex Pharmaceuticals Inc.

  公开号：EP1831168B1

  公开（公告）日：2014-07-02
• CASEIN KINASE 1delta (CK 1delta) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES SUCH AS TAUOPATHIES
  申请人：Electrophoretics Limited

  公开号：US20160354375A1

  公开（公告）日：2016-12-08

  The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1δ) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
• US4004012A
  申请人：——

  公开号：US4004012A

  公开（公告）日：1977-01-18